Objective To investigate the effects of different inspired oxygen concentrations on periop-erative cerebrovascular function in patients with a history of ischemic stroke.Methods A total of 150 patients scheduled for elective surgery with a history of ischemic stroke were enrolled from Renji Hospital,Shanghai Jiao Tong University School of Medicine,between June 2020 and March 2024.Using a random number table,patients were allocated into two groups:F30 group(intraoperative fraction of inspired oxygen,FiO2=30%)and F80 group(FiO2=80%),with 75 patients in each group.Bilateral middle cerebral artery(MCA)blood flow was continu-ously monitored using transcranial Doppler(TCD),including mean flow velocity(Vm),resistance index(RI),and pulsatility index(PI).Cerebral oxygen saturation(rScO2)was measured using a FORE-SIGHT oximeter.Arterial blood gas analysis was performed preoperatively,1 hour after induction,and before extubation to assess pH,partial pressure of arterial carbon dioxide(PaCO2),oxygenation index(OI),base excess(BE),hematocrit(Hct),and lactate(Lac).Peripheral blood samples were collected 24 hours postoperatively to measure thrombox-ane A2(TXA2)and prostacyclin(PGI2)levels.At 1 month postoperatively,telephone follow-up was conducted to evaluate the risk of recurrent cerebral ischemic events using the ABCD2 score and Essen Stroke Risk Score(ESRS).Results No significant differences were observed in baseline characteristics between the two groups.Perioperative arterial blood gas parameters did not differ significantly between groups(P>0.05).Compared with the F30 group,the F80 group exhibited a smaller reduction in mean flow velocity(Vm)of the affected MCA at the end of surgery(8.18%±3.34%vs.13.57%±5.32%,P<0.05),while no significant intergroup differences were found in RI or PI.At 1 hour after induction and before extubation,rScO2 of the affected hemisphere was signifi-cantly increased in the F80 group as compared with the F30 group(P<0.05),whereas no significant difference was observed in the contralateral hemisphere.Before extubation and on postoperative day 1,TXA2 levels were significantly lower and PGI2 levels higher in F80 group compared with F30 group(P<0.05).The proportion of patients at high risk of cerebral ischemia by ABCD2 and ESRS at 1 month postoperatively did not differ between groups(P>0.05).Conclusion In patients with a history of stroke,intraoperative administration of 80%FiO2under general anesthesia better maintains perioperative cerebral hemodynamic stability and cerebral oxygen satura-tion,improves cerebrovascular endothelial function,but does not significantly affect the short-term incidence of postoperative cerebrovascular events compared with 30%FiO2.

Objective:To explore the clinical phenotype and genetic characteristics of a patient with Progressive pseudorheumatoid dysplasia (PPRD) due to compound heterozygous variants of CCN6 gene. Methods:A patient who was admitted to Qilu Hospital of Shandong University due to " bilateral finger joint deformity, bilateral hip and knee joint movement limitation for 19 years" was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and her parents and subjected to whole exome sequencing (WES). Long-read sequencing (LRS) and Sanger sequencing were used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was classified. This study was approved by the Medical Ethics Committee of Qilu Hospital of Shandong University (Ethics No.: KYLL-202502 061).Results:The patient, a 23-year-old female, presented with progressive polyarticular deformity, limited movement and abnormal growth and development since childhood. She was initially misdiagnosed as Ankylosing spondylitis and had poor response to sulphasalazine and etoricoxib treatment. WES revealed that she has harbored two heterozygous variants of the CCN6 gene (NM_198239.2), namely c. 348C>A and c. 676G>C. LRS confirmed that the two variants are located on two homologous chromosomes and constitute compound heterozygous variants. Based on the ACMG guidelines, both variants were rated as pathogenic (PVS1+ PM2_Supporting+ PM3; PM1+ PM2_Supporting+ PM3_Supporting+ PM5+ PP3_Strong). The c. 676G>C variant has not been recorded by the HGMD and ClinVar databases. Conclusion:The c. 348C>A and c. 676G>C compound heterozygous variants of the CCN6 gene probably underlay the pathogenesis of PPRD in this patient. Above finding has enriched the mutational spectrum of PPRD and provided a basis for the clinical diagnosis and genetic counseling.

Objective To investigate the effect of extracorporeal diaphragmatic pacing(EDP)on wea-ning patients undergoing mechanical ventilation after acute Stanford type A aortic dissection(ATAAD)sur-gery.Methods A total of 80 patients who underwent ATAAD surgery and required mechanical ventilation in the cardiac intensive care unit(CCU)of our hospital from October 2023 to October 2024 were selected as the study subjects.They were randomly divided into a control group and an intervention group using a random number table method,with 40 patients in each group.Both groups of patients received conventional clinical drug therapy,mechanical ventilation support,and rehabilitation exercises after surgery.The intervention group additionally underwent EDP therapy on this basis.The clinical data,mechanical ventilation time,weaning out-comes,oxygenation index,tidal volume,and changes in diaphragm function parameters were compared be-tween two groups of patients.Results Compared with the control group,the intervention group had a shorter mechanical ventilation time[77.00(59.00,133.63)h]vs.54.50(49.00,105.25)h],offline success rate(72.5％vs.90.0％),oxygenation index[202.90(178.63,240.05)mmHg vs.236.50(196.00,293.75)mm-Hg],higher tidal volume[(496.00±111.95)mL vs.(563.23±133.98)mL],with a statistically significant difference(P＜0.05).Compared with the control group,diaphragmatic excursion(DE)of both sides[11.90(8.50,16.50)mm vs.15.30(12.20,19.80)mm;12.60(10.80,14.90)mm vs.14.70(11.43,19.20)mm]and diaphragmatic thickening fraction(DTF)of left and right side[21.75％(17.53％,27.13％)vs.26.30％(21.10％,32.40％);24.00％(17.68％,29.35％)vs.28.30％(22.43％,33.40％)]of the intervention group were higher,and the differences were statistically significant(P＜0.05).Conclusion EDP can enhance the function of the diaphragm in patients,shorten the duration of mechanical ventilation,improve the success rate of wea-ning,and improve the weaning outcomes of mechanically ventilated patients after ATAAD surgery.

OBJECTIVES: To investigate the effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) on glucose and lipid metabolism in mice with type 2 diabetes mellitus (T2DM) and circadian rhythm disorder (CRD) and explore the possible mechanisms. METHODS: KM mice were randomized into normal diet (ND) group (n=8), high-fat diet (HFD) group (n=8), and rhythm-intervention with HFD group (n=16). After 8 weeks of feeding, the mice were given an intraperitoneal injection of streptozotocin (100 mg/kg) to induce T2DM. The mice in CRD-T2DM group were further randomized into two equal groups for treatment with LCBE (225 mg/kg) or saline by gavage; the mice in ND and HFD groups also received saline gavage for 8 weeks. Blood glucose level of the mice was measured using a glucometer, and serum levels of Bmal1, PER2, insulin, C-peptide and lipids were determined with ELISA. Colon morphology and hepatic lipid metabolism of the mice were examined using HE staining and Oil Red O staining, respectively, and fecal short-chain fatty acids (SCFAs) was detected using LC-MS; GPR43 and GLP-1 expression levels were analyzed using RT-qPCR and Western blotting. RESULTS: Compared with those in CRD-T2DM group, the LCBE-treated mice exhibited significant body weight loss, lowered levels of PER2, insulin, C-peptide, total cholesterol (TC) and LDL-C, and increased levels of Bmal1 and HDL-C levels. LCBE treatment significantly increased SCFAs, upregulated GPR43 and GLP-1 expressions at both the mRNA and protein levels, and improved hepatic steatosis and colon histology. CONCLUSIONS LCBE ameliorates lipid metabolism disorder in CRD-T2DM mice by reducing body weight and improving lipid profiles and circadian regulators possibly via the SCFAs/GPR43/GLP-1 pathway.
Animals ; Mice ; Lipid Metabolism ; Diabetes Mellitus, Type 2/metabolism* ; Enterococcus faecium ; Glucagon-Like Peptide 1/metabolism* ; Bacillus subtilis ; Diabetes Mellitus, Experimental/metabolism* ; Circadian Rhythm ; Blood Glucose/metabolism* ; Receptors, G-Protein-Coupled/metabolism* ; Fatty Acids, Volatile/metabolism* ; Male ; Chronobiology Disorders/metabolism*

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a patient with Progressive pseudorheumatoid dysplasia (PPRD) due to compound heterozygous variants of CCN6 gene. METHODS: A patient who was admitted to Qilu Hospital of Shandong University due to "bilateral finger joint deformity, bilateral hip and knee joint movement limitation for 19 years" was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and her parents and subjected to whole exome sequencing (WES). Long-read sequencing (LRS) and Sanger sequencing were used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was classified. This study was approved by the Medical Ethics Committee of Qilu Hospital of Shandong University (Ethics No.: KYLL-202502 061). RESULTS: The patient, a 23-year-old female, presented with progressive polyarticular deformity, limited movement and abnormal growth and development since childhood. She was initially misdiagnosed as Ankylosing spondylitis and had poor response to sulphasalazine and etoricoxib treatment. WES revealed that she has harbored two heterozygous variants of the CCN6 gene (NM_198239.2), namely c.348C>A and c.676G>C. LRS confirmed that the two variants are located on two homologous chromosomes and constitute compound heterozygous variants. Based on the ACMG guidelines, both variants were rated as pathogenic (PVS1+PM2_Supporting+PM3; PM1+PM2_Supporting+PM3_Supporting+PM5+PP3_Strong). The c.676G>C variant has not been recorded by the HGMD and ClinVar databases. CONCLUSION The c.348C>A and c.676G>C compound heterozygous variants of the CCN6 gene probably underlay the pathogenesis of PPRD in this patient. Above finding has enriched the mutational spectrum of PPRD and provided a basis for the clinical diagnosis and genetic counseling.
Humans ; Female ; CCN Intercellular Signaling Proteins/genetics* ; Phenotype ; Heterozygote ; Young Adult ; Mutation ; Exome Sequencing ; Joint Diseases/congenital*

Objective To investigate the effects of different inspired oxygen concentrations on periop-erative cerebrovascular function in patients with a history of ischemic stroke.Methods A total of 150 patients scheduled for elective surgery with a history of ischemic stroke were enrolled from Renji Hospital,Shanghai Jiao Tong University School of Medicine,between June 2020 and March 2024.Using a random number table,patients were allocated into two groups:F30 group(intraoperative fraction of inspired oxygen,FiO2=30%)and F80 group(FiO2=80%),with 75 patients in each group.Bilateral middle cerebral artery(MCA)blood flow was continu-ously monitored using transcranial Doppler(TCD),including mean flow velocity(Vm),resistance index(RI),and pulsatility index(PI).Cerebral oxygen saturation(rScO2)was measured using a FORE-SIGHT oximeter.Arterial blood gas analysis was performed preoperatively,1 hour after induction,and before extubation to assess pH,partial pressure of arterial carbon dioxide(PaCO2),oxygenation index(OI),base excess(BE),hematocrit(Hct),and lactate(Lac).Peripheral blood samples were collected 24 hours postoperatively to measure thrombox-ane A2(TXA2)and prostacyclin(PGI2)levels.At 1 month postoperatively,telephone follow-up was conducted to evaluate the risk of recurrent cerebral ischemic events using the ABCD2 score and Essen Stroke Risk Score(ESRS).Results No significant differences were observed in baseline characteristics between the two groups.Perioperative arterial blood gas parameters did not differ significantly between groups(P>0.05).Compared with the F30 group,the F80 group exhibited a smaller reduction in mean flow velocity(Vm)of the affected MCA at the end of surgery(8.18%±3.34%vs.13.57%±5.32%,P<0.05),while no significant intergroup differences were found in RI or PI.At 1 hour after induction and before extubation,rScO2 of the affected hemisphere was signifi-cantly increased in the F80 group as compared with the F30 group(P<0.05),whereas no significant difference was observed in the contralateral hemisphere.Before extubation and on postoperative day 1,TXA2 levels were significantly lower and PGI2 levels higher in F80 group compared with F30 group(P<0.05).The proportion of patients at high risk of cerebral ischemia by ABCD2 and ESRS at 1 month postoperatively did not differ between groups(P>0.05).Conclusion In patients with a history of stroke,intraoperative administration of 80%FiO2under general anesthesia better maintains perioperative cerebral hemodynamic stability and cerebral oxygen satura-tion,improves cerebrovascular endothelial function,but does not significantly affect the short-term incidence of postoperative cerebrovascular events compared with 30%FiO2.

Objective:To explore the clinical phenotype and genetic characteristics of a patient with Progressive pseudorheumatoid dysplasia (PPRD) due to compound heterozygous variants of CCN6 gene. Methods:A patient who was admitted to Qilu Hospital of Shandong University due to " bilateral finger joint deformity, bilateral hip and knee joint movement limitation for 19 years" was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and her parents and subjected to whole exome sequencing (WES). Long-read sequencing (LRS) and Sanger sequencing were used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was classified. This study was approved by the Medical Ethics Committee of Qilu Hospital of Shandong University (Ethics No.: KYLL-202502 061).Results:The patient, a 23-year-old female, presented with progressive polyarticular deformity, limited movement and abnormal growth and development since childhood. She was initially misdiagnosed as Ankylosing spondylitis and had poor response to sulphasalazine and etoricoxib treatment. WES revealed that she has harbored two heterozygous variants of the CCN6 gene (NM_198239.2), namely c. 348C>A and c. 676G>C. LRS confirmed that the two variants are located on two homologous chromosomes and constitute compound heterozygous variants. Based on the ACMG guidelines, both variants were rated as pathogenic (PVS1+ PM2_Supporting+ PM3; PM1+ PM2_Supporting+ PM3_Supporting+ PM5+ PP3_Strong). The c. 676G>C variant has not been recorded by the HGMD and ClinVar databases. Conclusion:The c. 348C>A and c. 676G>C compound heterozygous variants of the CCN6 gene probably underlay the pathogenesis of PPRD in this patient. Above finding has enriched the mutational spectrum of PPRD and provided a basis for the clinical diagnosis and genetic counseling.

Objective: To investigate the effect of Guangdong Shenqu (GSQ) on intestinal flora structure in mice with food stagnation through 16S rDNA sequencing. Methods: Mice were randomly assigned to control, model, GSQ low-dose (GSQL), GSQ medium-dose (GSQM), GSQ high-dose (GSQH), and lacidophilin tablets (LAB) groups, with each group containing 10 mice. A food stagnation and internal heat mouse model was established through intragastric administration of a mixture of beeswax and olive oil (1:15). The control group was administered normal saline, and the model group was administered beeswax and olive oil to maintain a state. The GSQL (2 g/kg), GSQM (4 g/kg), GSQH (8 g/kg), and LAB groups (0.625 g/kg) were administered corresponding drugs for 5 d. After administration, 16S rDNA sequencing was performed to assess gut microbiota in mouse fecal samples. Results: The model group exhibited significant intestinal flora changes. Following GSQ administration, the abundance and diversity index of the intestinal flora increased significantly, the number of bacterial species was regulated, and α and β diversity were improved. GSQ administration increased the abundance of probiotics, including Clostridia, Lachnospirales, and Lactobacillus, whereas the abundance of conditional pathogenic bacteria, such as Allobaculum, Erysipelotrichaceae, and Bacteroides decreased. Functional prediction analysis indicated that the pathogenesis of food stagnation and GSQ intervention were primarily associated with carbohydrate, lipid, and amino acid metabolism, among other metabolic pathways. Conclusion The digestive mechanism of GSQ may be attributed to its role in restoring diversity and abundance within the intestinal flora, thereby improving the composition and structure of the intestinal flora in mice and subsequently influencing the regulation of metabolic pathways.

ObjectiveTo study the effect and mechanism of Linggui Zhugantang in treating chronic bronchitis （CB） induced by exposure to cigarette smoke combined with tracheal instillation of lipopolysaccharide （LPS）. MethodSixty SPF-grade SD rats were randomly divided into normal， model， dexamethasone （1 mg·kg^-1）， and high-， medium-， and low-dose （30.06， 15.03， 7.515 g·kg^-1， respectively） Linggui Zhugantang groups by the body weight stratification method， with 10 rats in each group. Each group was administrated with 200 μL LPS （1 g·L^-1） by tracheal instillation on days 1 and 14， respectively， while the normal group was administrated with an equal volume of normal saline. Except the normal group， the other groups were exposed to cigarette smoke on days 2-13 and 15-30 （10 cigarettes/time/30 min， twice/day） for the modeling of CB. The rats were administrated with corresponding drugs by gavage for 30 consecutive days from day 2 of modeling， and the mental status， behavior， and body weights of the rats were observed and measured. The wet/dry mass ratio （W/D） of the left lung was measured 30 days after modeling. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung and bronchial tissues. The bronchial mucus secretion and goblet cell proliferation were observed by Alcian blue-periodic acid Schiff （AB-PAS） staining. The levels of mucin 5AC （MUC5AC）， interleukin （IL）-13， IL-6， and tumor necrosis factor （TNF）-α in the serum were determined by enzyme-linked immunosorbent assay. The expression of phospholipase A2 （PLA2）， transient receptor potential vanilloid receptor 1 （TRPV1）， and transient receptor potential ankyrin 1 （TRPA1） in the lung tissue was quantitatively analyzed by immunohistochemistry and Western blot. ResultCompared with the normal group， the model group showcased abnormal mental status and behaviors， bloody secretion in the nose and mouth， the mortality rate of 40%， decreased body weight， severe lung bronchial structure damage， a large number of inflammatory mediators and inflammatory cell infiltration in the tube wall， hyperemia， edema， and fibroplasia， massive proliferation of goblet cells， excessive secretion and accumulation of mucus， stenosis and deformation of the lumen， and aggravation of pulmonary edema （P<0.01）. In addition， the model group had higher levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and higher expression of PLA2 in the lung tissue than the normal group （P<0.01）. Compared with the model group， the medication groups showed normal mental status and behaviors， reduced mortality rate， stable weight gain， reduced lung and bronchial injuries， decreased goblet cell proliferation and mucus secretion， and alleviated pulmonary edema （P<0.01）. Furthermore， Linggui Zhugantang lowered the levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and down-regulated the protein levels of PLA2， TRPV1， and TRPA1 in the lung tissue （P<0.01）. ConclusionLinggui Zhugantang can reduce the pulmonary inflammation and airway mucus hypersecretion in the rat model of chronic bronchitis. It may exert the effects of reducing inflammation and resolving phlegm by regulating the PLA2-TRPV1/TRPA1 pathway.

Anti γ-aminobutyric acid B receptor encephalitis is a type of autoimmune encephalitis characterized by the production of self specific antibodies in cerebrospinal fluid and/or serum, with seizures, memory loss, and consciousness disorders as the main clinical manifestations. This type of encephalitis caused by autoantibodies has the same pathological characteristics as other peripheral encephalitis. There are many different etiologies and pathophysiological processes that lead to the occurrence of limbic encephalitis, and it is necessary to understand their heterogeneity in order to find effective treatment methods. This article will systematically review the epidemiology, pathogenesis, clinical characteristics, diagnosis, treatment, and prognosis of anti γ-aminobutyric acid B receptor encephalitis, aiming to enhance clinical doctors' understanding of this disease and provide reference for clinical decision-making.